Potassium Carbonate → 4-methylphenyl 5-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoate

HRID 2048095Notes

Reaction equation

HRID 2048095 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:15])[CH:5]=[N:6][C:7]=1[O:8][C@@H:9]([CH3:14])[C:10]([F:13])([F:12])[F:11].[Cl:16][C:17]1[C:18](F)=[CH:19][C:20]([F:33])=[C:21]([CH:32]=1)[C:22]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)=[O:23].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[Cl:16][C:17]1[C:18]([O:15][C:4]2[CH:5]=[N:6][C:7]([O:8][C@@H:9]([CH3:14])[C:10]([F:11])([F:12])[F:13])=[C:2]([Cl:1])[CH:3]=2)=[CH:19][C:20]([F:33])=[C:21]([CH:32]=1)[C:22]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)=[O:23]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 580424575-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-olHCID 58042518HCID 58042518, compound

Product 1

HCID 580425084-methylphenyl 5-chloro-4-({5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoateYield 86%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 5-chloro-6-[(1S)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-ol (Preparation 231, 60 mg, 0.25 mmol) and 4-methylphenyl 5-chloro-2,4-difluorobenzoate (Preparation 26, 70 mg, 0.25 mmol) in DMSO (1 mL) was added K2CO3 (69 mg, 0.50 mmol) at room temperature under N2 and the resulting mixture was stirred for 4 hours. The reaction mixture was warmed up to 50° C. and stirred for 1 hour before cooling to room temperature and stirring for 18 hours. The reaction was quenched with water and partitioned between water and DCM (3×5 mL). The mixture was filtered through a phase separation cartridge, the organic phase was washed with brine (3 mL) and filtered through another phase separation cartridge. The filtrate was dried by N2 blowing to give a crude product that was purified by silica gel column chromatography eluting with 0-20% EtOAc in heptane to give the title compound (108 mg, 86%) as colourless gum.

Workup

  1. stirringstirred for 1 hour
  2. temperaturebefore cooling to room temperature
  3. stirringstirring for 18 hours
  4. customThe reaction was quenched with water
  5. custompartitioned between water and DCM (3×5 mL)
  6. filtrationThe mixture was filtered through a phase separation cartridge
  7. washthe organic phase was washed with brine (3 mL)
  8. filtrationfiltered through another phase separation cartridge
  9. dry with materialThe filtrate was dried by N2 blowing
  10. customto give a crude product that
  11. customwas purified by silica gel column chromatography
  12. washeluting with 0-20% EtOAc in heptane

Sources & evidence

ORD record
ord-a23c49f04771439aaea773e56d122fe5
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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